DE102014107837A1 - Optical sensor for the quantitative detection of an analyte in a sample and method for producing the sensor - Google Patents

Abstract

A sensor (1) for the quantitative detection of an analyte in a sample (7) is disclosed. The sensor (1) comprises a medium (3) with a dye (2), which has an optical behavior that can be influenced by the analyte within the sensor (1). The sensor (1) has an osmolality in the medium (3), which is greater than a predetermined maximum Probenosmolalität, for which the sensor (1) is provided. The medium (3) is located inside the sensor (1) in at least one hollow fiber section (4). The interaction of the at least one hollow fiber section (4), which mechanically impedes swelling of the medium (3), and the predetermined osmolality in the medium (3) results in a reduced cross-sensitivity of the sensor (1) with respect to sample osmolality. Furthermore, a method for producing a sensor (1) according to the invention is disclosed. At least one hollow fiber (5) is filled with the dye (2) containing medium (3) and divided into hollow fiber sections (4).

Description

The invention relates to a sensor for the quantitative detection of an analyte in a sample, in which an optical behavior of at least one dye is used for the quantitative detection of the analyte. Furthermore, the invention relates to a method for producing such a sensor.

The translation DE 694 30 003 T2 the European patent specification EP 0 731 664 B1 for international registration PCT / US94 / 12146 discloses a sensor with an indicator dye contained in an aqueous phase. The dye may be in a particle ad- or in particles absorbed liquid, the particles in turn are embedded in a gas and translucent polymeric material, which does not pass liquid water. The aqueous phase may also be enclosed in microcompartments. Further, the aqueous phase may contain a buffer and salts to set a desired osmolarity.

The international publication WO 00/26655 A1 the international application PCT / US99 / 25506 discloses a dye entrapped in a well of a sensor membrane. A perforated metal disc is placed under the sensor membrane to prevent swelling of the dye layer.

The German translation DE 692 19 061 T2 the European patent specification EP 0 539 175 B1 describes inter alia the impregnation of a carrier with a reagent composition. This contains a buffer and may contain as binders such as cellulose, gum arabic or polyvinylpyrrolidone.

The German translation DE 696 12 017 T2 the European patent specification EP 0 873 517 B1 for international registration PCT / US96 / 16469 describes an aqueous phase with indicator and buffer which is in a second hydrophobic phase. This emulsion may contain humectants. The aqueous phase is in microcompartments. It is possible to add substances which regulate the osmotic pressure.

The German patent application DE 2 134 910 relates to a dye for staining white blood cells and a method for the analytical determination of white blood cells in the blood. An aqueous solution containing a dye is spiked with a blood sample. In this case, the aqueous solution contains additives to maintain a pH and an osmolality within the normal ranges for human blood plasma.

The international publication WO 2009/140559 A1 for international registration PCT / US2009 / 044048 discloses a sensor element with a layered structure. An indicator is bound to a porous support membrane which is arranged on a polymer substrate. The support membrane may also be made of plastic fabric.

The US publication US 2004/171094 A1 refers to a dye included in hydrophobic polymer particles with analyte-dependent phosphorescence. The particles may in turn be embedded in a layer or matrix which may be water-absorbent and swell when absorbed by water.

The US publication US 2008/215254 A1 describes sensors which consist of one or more layers arranged on a transparent carrier. The layers may consist of a polymer and be arranged for example in the wells of a microtiter plate or at the end of a light guide.

Optical sensors for detecting acidic or basic gases, for example ammonia or sulfur dioxide, dissolved in gaseous samples or in liquids, are well known. These sensors have a dye with an optical behavior that is affected by the gas to be detected, often indirectly, such as by a change in the pH of a buffer solution containing the dye. In general, the buffer solution with the dye is separated from the sample to be examined by a gas-permeable material, for example a gas-permeable polymer. Now, if water from the sample in the buffer solution, because the gas-permeable material itself is water-receptive and water then passes from the gas-permeable material into the buffer solution, or because water diffused in the form of vapor through the gas-permeable material in the buffer solution, the concentration changes of the buffer and thus the pH. This results in conditions in the sensor, which no longer correspond to the calibration of the sensor. Since the water transport into the buffer solution is determined by the osmolality of the buffer solution and the sample, the sensor exhibits an osmolality cross sensitivity. This is especially problematic if the osmolality of the sample changes over the duration of a measurement. This problem occurs, for example, in the biotechnology sector, where sensors of the type described are used for monitoring bioprocesses, such as fermentations or cell cultivations. Also in the medical field, in online or offline measurements in blood, urine or tissues, strong changes in osmolality can occur, which in the described sensors according to the prior art lead to large measurement errors.

The object of the invention is to provide a sensor which has a reduced Osmolalitätsquerempfindlichkeit compared to the prior art, and its calibration is thus largely independent of the osmolality of the sample.

This object is achieved by a sensor according to claim 1.

A further object of the invention is to provide a method with which a sensor can be produced which has a reduced osmolality cross-sensitivity compared to the prior art, and whose calibration is thus largely independent of the osmolality of the sample.

This object is achieved by a method according to claim 16.

The sensor according to the invention for the quantitative detection of an analyte in a sample comprises at least one dye which has an optical behavior which can be influenced by the analyte within the sensor, which therefore depends directly or indirectly on the analyte, due to the design of the sensor. This means that the analyte can be quantitatively deduced from the optical behavior of the at least one dye, so that it is possible, for example, to determine a concentration or a partial pressure for the analyte. For this purpose, a calibration of the sensor is advantageously used. By quantitative detection of the analyte is meant that a value for the concentration or the partial pressure of the analyte is determined up to standard error limits, but also that it is only determined that the concentration or the partial pressure of the analyte are within a predetermined range; the predetermined range may have a lower limit and an upper limit, or only one of a lower limit and an upper limit.

Furthermore, the sensor according to the invention comprises a medium in which the at least one dye is contained; for example, the medium may comprise a liquid in which the at least one dye is dissolved; Depending on the embodiment, the medium may include further components, as will be explained below.

According to the invention, the sensor comprises at least one hollow fiber section, in the interior of which the medium containing the dye is present, and also according to the invention an osmolality is given in the medium, which is greater than a predetermined maximum sample osmolality, for which a use of the sensor is provided. For samples with an osmolality greater than this maximum sample osmolality, the sensor according to the invention should not be used, since the measurement results in such a case would not be reliable. In a preferred embodiment, the sensor comprises a plurality of hollow fiber sections, in the interior of which the medium is located.

The at least one hollow fiber section causes a mechanical restriction of a change in volume of the medium. The combination of this mechanical restriction with the given osmolality in the medium results in a defined uptake of solvent, for example water, into the medium when the sensor is brought into contact with a sample in which the analyte, ie the substance to be detected, in the Solvent is dissolved. For gaseous samples, water in the form of water vapor contained in the sample can correspondingly pass into the sensor, and analogously a defined uptake of water results. As long as the osmolality in the medium is greater than in the sample, the osmotic pressure acts on an inflow of the solvent into the medium. This influx of solvent would cause the medium to swell. Due to the at least one hollow fiber section, the change in volume of the medium, ie in particular a swelling, but sharply limited; This also clearly limits the uptake of solvent into the medium. As a result, for a given sensor, there will be a defined uptake of solvent into the medium, regardless of the osmolality of the sample, as long as the osmolality of the sample is less than the osmolality in the medium. This defined uptake of solvent can be taken into account when calibrating the sensor. Thus, a calibration of the sensor is independent of the osmolality of the sample in which the sensor is used as long as the osmolality of the sample is less than the osmolality in the medium.

In one embodiment of the sensor according to the invention, the at least one dye is mixed with a buffer solution, which is then regarded as part of the medium. This is mainly used in those sensors in which the sensor effect is based on a pH-dependent optical behavior of the at least one dye, and the analyte causes a pH change in the medium.

The osmolality in the medium can be adjusted in the manufacture of the sensor by adding at least one substance to the medium. In embodiments, the at least one substance may be mixed with the at least one dye. As substances for adjusting the osmolality in the medium, for example, salts, such as NaCl or KCl, polyelectrolytes or neutral molecules such as sugars, such as glucose, fructose, mannose, sucrose, can be used. These added substances are also part of the To look at the medium. It is of course important that the added substances do not interfere with the quantitative detection of the analyte.

The optical behavior of the dye, which is used for the quantitative detection of an analyte, may be, for example, a luminescence, wherein luminescence comprises at least phosphorescence and fluorescence. Likewise, a light reflection or light absorption can be used for the quantitative detection of the analyte. Another option is to use one color of the dye. In each case, the color of the dye, the light reflection or absorption, or the luminescence show a dependence on the analyte. In the case of a luminescence, this dependence may be that a relaxation time of the luminescence, which may be a relaxation time for the intensity of the luminescence or for a polarization of the luminescence, depends on the analyte. Likewise, it is conceivable that the intensity or wavelength of the luminescent light that occurs will depend on the analyte. In the case of one color, the dye may take on a different color depending on the concentration or partial pressure of the analyte. In the case of light reflection or absorption, the reflectivity or the degree of absorption of a layer containing the dye for certain wavelengths of light may change depending on the analyte. It is also possible to exploit more than one type of optical behavior for the measurement, for example a relaxation time of the luminescence and an absorption behavior. For this purpose, more than one dye can be used so that, for example, the luminescence behavior of a first dye and the absorption behavior of a second dye are evaluated in order to quantitatively determine an analyte. If more than one dye is used, the efficiency of nonradiative energy transfer between the dyes, for example the Förster resonance energy transfer, as far as this efficiency is quantitatively dependent on the analyte, can also be used for the quantitative determination of the analyte.

The dependence of the optical behavior on the analyte may result from a direct interaction between the analyte and the at least one dye, such as an energy exchange or chemical reaction between molecules of the dye and the analyte, or substances added via the dye from an indirect interaction. Generic requirement for the functioning of the sensor is that the analyte with the at least one dye in such a direct or indirect interaction can occur. In a sensor according to the invention, in which, for example, dye and buffer solution are present in the interior of the at least one hollow fiber section, the analyte must be able to reach the mixture of dye and buffer solution.

Examples of analytes are gases in gaseous mixtures or gases dissolved in liquids. For example, dissolved in water gas, such as sulfur dioxide, carbon dioxide, carbon monoxide or ammonia can be detected by a sensor according to the invention. Thus, the ammonia reacting in water is an example in which a dye with a pH-dependent optical behavior can be selected as the dye for the sensor. Depending on the concentration of the ammonia dissolved in the sample, a pH is established within the medium, which can be determined from the optical behavior of the dye. Indirectly such a conclusion on the ammonia concentration is possible. Of course, a direct calibration of the ammonia concentration against the optical behavior is possible, an actual determination of a pH value is then not required. The above example of ammonia detection is also an example of an indirect interaction between the dye and the analyte, in this case the ammonia. The interaction occurs here via a buffer solution mixed with the dye, in that the analyte changes the pH of the buffer solution, and the optical behavior of the dye depends on the pH of its environment, in this case the buffer solution. Analogous statements also apply to sulfur dioxide and other gases. An example of a dye with a pH-dependent fluorescence behavior with which to detect carbon dioxide is hydroxypyrene trisulfonic acid (HPTS). For measuring sulfur dioxide, for example, bromocresol red can be used. For the quantitative detection of ammonia, bromothymol blue or bromophenol blue can be used. Numerous other dyes and their potential applications for the quantitative detection of a wide variety of substances are well known to the person skilled in the art.

It should also be pointed out that various possibilities are known for the explicit quantitative determination of the analyte from the optical behavior of the at least one dye via a corresponding calibration. For example, a relaxation time of a luminescence of the at least one dye can be calibrated against partial pressure or concentration of the analyte. Instead of using the relaxation time itself, variables dependent thereon can also be used, such as quotients of integrals over the time course of luminescence signals or phase shifts between a modulated excitation signal and the luminescence response of the dye. These and other possibilities are adequately described in the prior art, for example in German Patent application DE 10 2011 055 272 A1 and the writings quoted therein.

However, sensors according to the invention can also be used for the quantitative detection of other solutes, including ions.

In one embodiment of the sensor according to the invention, the at least one hollow fiber section is embedded in a carrier substance. Preferably, a plurality of hollow fiber sections is used, and the carrier fixes the hollow fiber sections relative to each other. In this case, the analyte must be able to pass through the carrier to the medium inside the at least one hollow fiber section. This can be done, for example, by diffusion of the analyte into the carrier substance. In this context, in one embodiment, the carrier substance is gas-permeable. In embodiments, the vehicle is hydrophobic. In specific embodiments, the carrier substance is a polymer or a silicone.

In a specific embodiment, the sensor includes a hygroscopic substance. Such embodiments can be used in gaseous samples, such as in the atmosphere. The hygroscopic substance absorbs water from the sample, which is present in the sample as water vapor. Thus, an aqueous environment is generated for the at least one dye. Thus, dyes and additives such as buffers may be used, which are otherwise limited to aqueous samples to make measurements in the gas phase. Preferably, the hygroscopic substance is mixed with the at least one dye.

In certain embodiments of the sensor according to the invention, the at least one hollow fiber portion is made of glass, i. it is a section of a glass hollow fiber. Glass has a sufficiently high mechanical stability to effectively mechanically limit the swelling of the medium due to the osmotic pressure. However, it is also possible to use other materials for the hollow fibers which have sufficient mechanical stability to effectively limit the swelling of the medium mechanically. An effective mechanical restriction of the swelling of the medium is understood to mean that the volume change of the medium caused by the osmotic pressure is limited to a value at which a measurement error caused by this volume change remains below a value defined by the manufacturer or user of the sensor. for example, a relative measurement error of less than 5%, preferably less than 1% and particularly preferably less than 0.1%.

In another embodiment of the sensor according to the invention, the hollow fiber sections are not fixed in a carrier substance, but intended to be dispersed in a sample. The hollow fiber sections are then movable within the sample. In particular, the hollow fiber sections in the sample may float or float. Preferably, the ends of the hollow fiber sections are thereby closed, and the material of the hollow fiber sections themselves is permeable to the analyte. Hollow-fiber sections of material permeable to the analyte are, of course, also conceivable in embodiments in which the at least one hollow-fiber section is embedded in a carrier substance. In this case, the ends of the at least one hollow fiber section may be open or closed.

Regardless of whether the at least one hollow fiber section is embedded in a carrier substance or intended to be introduced directly into a sample, the ends of the at least one hollow fiber section can be closed by a respective stopper. Such a plug may consist of an adhesive, a polymer, a silicone or a wax. The ends of the at least one hollow fiber section may also be closed by caps; such caps can for example be glued to the hollow fiber portion, or merely attached to the ends of the hollow fiber portion and frictionally supported there sein.Diese options for closing the ends of the at least one hollow fiber portion are always possible in principle, but are particularly suitable for hollow fiber sections, which made of glass or a non-thermoplastic material such as polyurethane (PU) or polytetrafluoroethylene (PTFE) exist. The material of the plugs or caps may be permeable to the analyte.

Alternatively, the at least one hollow fiber portion itself may be shaped such that the ends of the at least one hollow fiber portion are closed. If the hollow fiber sections consist of a thermoplastic material such as, for example, polypropylene (PP), polyethylene (PE), polyvinylidene fluoride (PVDF) or polyethersulfone (PES), the ends of a hollow fiber section can be closed by squeezing with a tool of sufficiently high temperature. In this context, a temperature is then sufficiently high if the respective plastic is plastically deformable at this temperature, so that the material of the hollow fiber section can be deformed by the tool; the temperature required for this depends on the particular plastic. The deformation of the material of the hollow fiber section at the ends of the hollow fiber section results in the described case in a form of the Hollow fiber portion in which the ends of the hollow fiber portion are closed.

The method according to the invention for producing a sensor for quantitatively detecting an analyte in a sample comprises the following steps:
At least one hollow fiber is filled with a medium. The medium is of the type described above, that is, the medium contains at least one dye which has an optical behavior that can be influenced by the analyte within the sensor, and the medium has an osmolality which is greater than a predetermined one maximum sample osmolality for which the sensor is intended.

The at least one, now filled, hollow fiber is divided into hollow fiber sections. The cutting can be done for example by cutting, sawing, punching or breaking. If the hollow fiber consists of a thermoplastic, then the dicing of the hollow fiber can also be effected by squeezing off portions of the hollow fiber from the remainder of the hollow fiber through a tool of sufficiently high temperature. At the same time, the ends of the resulting hollow fiber sections are deformed, so that the ends of these hollow fiber sections are closed. In this context, a temperature is then sufficiently high if the respective plastic is plastically deformable at this temperature, so that the material of the hollow fiber can be deformed by the tool; the temperature required for this depends on the particular plastic. As a tool for squeezing, for example, a wire can be used; the wire can be brought to a required temperature by means of an electric current forced through it and kept at this temperature.

The hollow fiber sections are mixed with a carrier, such as by stirring; the carrier substance is present in a fluid form, for example as a gel or as a liquid. The mixture of hollow fiber sections and carrier substance is distributed over a surface, finally the carrier substance is cured. The hollow fiber sections are thus fixed in the carrier substance.

The surface over which the mixture of hollow fiber sections and carrier substance is distributed may be the surface of a plate which is to function as a carrier plate for the sensor. It is conceivable that the mixture of hollow fiber sections and carrier substance is distributed over a large area over a plate, the carrier is then cured, and then obtained from the plate individual sensors such as by cutting, sawing, punching or breaking. In the plate predetermined breaking points can be provided.

In embodiments of the method, the carrier substance is a polymer or a silicone. The curing of the carrier substance may in this case comprise the crosslinking of the polymer chains or silicone chains.

The fluid form of the carrier substance is formed in embodiments in that the carrier substance is dissolved in a solvent. The curing of the carrier substance is then effected by drying the solution of the carrier substance. In particular, the solvent can be evaporated off. If the carrier substance is a polymer or a silicone, the polymer or silicone may be dissolved, in particular, in an organic solvent which is evaporated off to cure the carrier substance. Examples of suitable solvents are toluene, tetrahydrofuran (THF), hexane, cyclohexane, chloroform and octane.

In accordance with the embodiments of the sensor according to the invention discussed above, the dye in the medium may be mixed with a buffer solution.

In embodiments of the method, capillary forces are used to fill the at least one hollow fiber. For this purpose, one end of the at least one hollow fiber is immersed in a supply of the medium. The capillary forces then draw media with dye into the interior of the hollow fiber. Depending on the configuration of the method, the filling of the at least one hollow fiber can be supported by additional measures, such as by pumping.

In one embodiment of the method, a multiplicity of hollow fibers are filled at the same time. The hollow fibers are present as a bundle. One end of the bundle and thus one end of the bundle forming hollow fibers is immersed in the supply of the medium. In this way, the hollow fibers are filled by utilizing capillary forces, as mentioned above. The medium penetrates into the bundle but also into the spaces between the hollow fibers, i. H. it is located after the filling medium on the outside of the hollow fibers. This is washed off in a subsequent step, but previously, in order to protect the medium inside the hollow fibers prior to the washing process, the ends of the hollow fibers are closed.

After washing the medium from the outside of the hollow fibers, the hollow fibers are cut into hollow fiber sections and further processed as previously described.

The medium may contain other substances. In particular, the method according to the invention allows the production of a sensor according to the invention.

In the following the invention will be discussed in more detail by means of embodiments with reference to the accompanying drawings.

1 shows a schematic sectional view of an embodiment of a sensor according to the invention.

2 schematically shows the filling of a hollow fiber.

3 schematically shows the filling of a bundle of hollow fibers.

4 schematically shows a hollow fiber section.

5 schematically shows a sensor according to the invention in a sample.

6 schematically shows an embodiment of the sensor according to the invention, in which the hollow fiber portions of the sensor are dispersed in a sample.

7 schematically shows a hollow fiber portion whose ends are closed by grafting.

8th schematically shows a hollow fiber portion whose ends are closed by caps.

9 schematically shows a hollow fiber portion which is shaped so that its ends are closed.

1 shows a sectional view of an embodiment of a sensor according to the invention 1 , Hollow fiber sections 4 are embedded in a carrier, which here is a polymer 10 is. The hollow fiber sections 4 are with a medium 3 filled. The medium contains a dye not explicitly shown here 2 which has optical behavior within the sensor 1 can be influenced by an analyte. The polymer 10 is on a backing plate 11 arranged. On the support plate 11 opposite side of the polymer 10 is the polymer 10 with a cover layer 12 covered.

For example, the carrier plate 11 for when measuring by means of the sensor 1 be transparent occurring light wavelengths. Is it the optical behavior of the dye 2 about a luminescence, so should the carrier plate 11 be transmissive to the light, which is used to excite the luminescence and permeable to the luminescent light. The cover layer is advantageous in this case 12 formed for the light used to excite the luminescence and reflective for the luminescence. Alternatively, of course, the cover layer 12 be transparent to the corresponding wavelengths of light, and then is the support plate 11 formed reflective for these wavelengths of light.

In any case, the polymer must 10 , and advantageously also the carrier plate 11 and / or the cover layer 12 be permeable to the analyte, so that the analyte is the medium 3 in the polymer 10 embedded hollow fiber sections 4 can reach.

The ends 4a and 4b of each hollow fiber section 4 are open in the embodiment shown. Through these open ends 4a and 4b is the medium 3 in the hollow fiber sections 4 definitely accessible as soon as the analyte enters the polymer 10 has penetrated. In addition, also the material of the hollow fiber sections 4 even be permeable to the analyte.

One layer thickness 15 the hollow fiber sections 4 containing layer of the carrier substance, here the polymer 10 , is in typical embodiments 200 microns to 300 microns; However, the invention is expressly not limited to this layer thickness range.

In principle, a sensor according to the invention can also be used without a carrier plate 11 and topcoat 12 In particular, the invention is not limited to the embodiment shown. However, the elements mentioned have advantages. So can a carrier plate 11 For example, made of glass or plastic, the layer of the polymer 10 with embedded hollow fiber sections 4 stabilize mechanically so that the sensor 1 easier to handle and more resistant to damage. Also the top layer 12 can provide mechanical protection for the layer of the polymer 10 form. A reflective layer formed for the luminescent light 12 increases the sensitivity of the method, since a higher intensity of the luminescent light is available for the evaluation when luminescent light from the cover layer 12 is reflected to a detector. The same applies to the case of a reflective formed carrier plate 11 ,

2 is a schematic representation of the filling of a hollow fiber 5 , An end 5a the hollow fiber 5 is in a supply of the medium 3 dipped. A storage container 12 for the medium 3 is shown symbolically. The medium 3 contains the dye 2 ,

Capillary forces become part of the medium 3 with colorant 2 in the hollow fiber 5 sucked. After completion of the filling process is one with medium 3 and dye 2 filled hollow fiber 5 before, which then in hollow fiber sections 4 can be divided.

3 corresponds largely to the 2 , only here is a bunch 6 of hollow fibers 5 with the the dye 2 containing medium 3 filled. Every hollow fiber 5 of the bunch 6 is with an end 5a into a supply of the medium 3 dipped. The bundle 6 can be a simple packing of hollow fibers 5 But it is also possible that the hollow fibers 5 in the bundle 6 twisted around each other, leaving the bundle 6 forms a kind of yarn.

Become several in a bundle 6 consolidated hollow fibers 5 filled, so penetrates medium 3 also in the spaces between the hollow fibers 5 in the bundle 6 one. Before dividing the filled hollow fibers 5 in hollow fiber sections 4 Therefore, the bundle is washed or rinsed to the in these spaces and thus on the outer sides of the hollow fibers 5 located medium 3 to remove. To the located inside the hollow fibers medium 3 to protect from the hollow fibers during the washing or rinsing process 5 to be removed again, the ends become 5a and 5b the hollow fibers 5 closed before the washing or rinsing process. The thus purified hollow fibers 5 are then in hollow fiber sections 4 divided.

4 shows a schematic representation of a section through an embodiment of a hollow fiber section 4 as it can be used in the sensor according to the invention. Inside the hollow fiber section 4 there is dye 2 containing medium 3 , The sensor according to the invention 1 comprises at least one hollow fiber section 4 For example, the embodiment shown here, preferably a plurality of hollow fiber sections 4 , In the method according to the invention are with medium 3 and dye 2 filled hollow fiber sections 4 in a carrier substance, for example a polymer 10 or a silicone, which is cured after application to a carrier. In one embodiment, an outer diameter is 16 such a hollow fiber section 10 microns to 12 microns, an inner diameter 17 between 5 μm and 6 μm, and one length 18 of the hollow fiber section between 0.5 mm and 1 mm. It should be emphasized that the invention is not limited to these dimensions of hollow fiber sections 4 is limited.

5 schematically shows a sample 7 in a sample container 13 , A sensor according to the invention 1 is inside the sample container 13 arranged and in contact with the sample 7 , In particular, in the sample 7 included with the sensor 1 to be detected analyte so in the polymer 10 , in the hollow fiber sections 4 and ultimately into the medium 3 arrive at the optical behavior of the medium in the medium 3 contained dye 2 to influence. Optical methods are used to study the optical behavior. Symbolically, here is an end of a light guide 14 shown. If the optical behavior is, for example, a luminescence phenomenon, the light guide can be used 14 Light for exciting the luminescence to the sensor 1 and ultimately to the dye 2 reach, and luminescent light can from the dye 2 over the light guide 14 be led to the evaluation.

6 shows a sample 7 in a sample container 13 , In the embodiment of the sensor according to the invention shown here 1 is the multitude of hollow fiber sections 4 of the sensor 1 in the sample 7 dispersed. In the embodiment shown, the ends are 4a . 4b the hollow fiber sections 4 closed and the material of the hollow fiber sections 4 is permeable to the analyte.

Furthermore, an exemplary measuring arrangement 20 shown, which for detecting the optical behavior of the hollow fiber sections 4 within the medium 3 contained at least one dye is provided. The measuring arrangement 20 includes a control and evaluation unit 22 , these associated light sources 24 and also the control and evaluation unit 22 associated camera 26 , The light sources 24 provide light for the evaluation of the optical behavior of the dye, for example, light to excite a luminescence of the dye. The control and evaluation unit 22 evaluates with the camera 26 taken pictures of the sample 7 including the sensor inside 1 and can thereby perform a quantitative determination of the analyte spatially resolved. The captured images contain information about the optical behavior, such as luminescence, of the dye in a respective hollow fiber section 4 at a particular location within the sample 7 , When evaluating the recorded images, the control and evaluation unit takes action 22 advantageous in the control and evaluation 22 stored calibration data 23 of the sensor 1 back.

The exemplary measuring arrangement 20 shows a principle possibility, such as an embodiment of the sensor according to the invention 1 can be used. However, the sensor according to the invention is not limited to use with a measuring arrangement of the type shown. Important for the use of the sensor according to the invention is merely that an analyte-dependent optical behavior of the in the at least one hollow fiber section 4 located dye can be examined.

7 schematically shows an embodiment of a hollow fiber section 4 , as it can be used in the sensor according to the invention. Inside the hollow fiber section 4 there is dye 2 containing medium 3 , In the hollow fiber section shown 4 are the ends 4a and 4b of the hollow fiber section 4 each by a plug 4c locked.

8th schematically shows a further embodiment of a hollow fiber section 4 , as it can be used in the sensor according to the invention. Inside the hollow fiber section 4 there is dye 2 containing medium 3 , In the hollow fiber section shown 4 are the ends 4a and 4b of the hollow fiber section 4 each by a cap 4d locked. The cap 4d For example, with the hollow fiber section 4 be glued. It is also conceivable that the caps 4d on the ends 4a respectively. 4b of the hollow fiber section 4 are plugged and held there frictionally.

9 schematically shows a further embodiment of a hollow fiber section 4 , as it can be used in the sensor according to the invention. Inside the hollow fiber section 4 there is dye 2 containing medium 3 , The hollow fiber section shown 4 has a shape through which the ends 4a and 4b of the hollow fiber section 4 are closed. Such a shape can, for example, by plastic deformation of the material of the hollow fiber section 4 be formed. For this purpose, the material of the hollow fiber section 4 locally exposed to an elevated temperature, such as by using a heated tool for deformation. The temperature mentioned must be so high that the material of the hollow fiber section 4 is plastic at this temperature. In particular, this procedure is possible if the hollow fiber section 4 made of a thermoplastic material. Of course, due to the elevated temperature neither the dye should 2 still components of the medium 3 damaged so far that the functionality of the sensor is impaired.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• DE 69430003 T2 [0002]
• EP 0731664 B1 [0002]
• US94 / 12146 [0002]
• WO 00/26655 A1 [0003]
• US 99/25506 [0003]
• DE 69219061 T2 [0004]
• EP 0539175 B1 [0004]
• DE 69612017 T2 [0005]
• EP 0873517 B1 [0005]
• US 96/16469 [0005]
• DE 2134910 A [0006]
• WO 2009/140559 A1 [0007]
• US 2009/044048 [0007]
• US 2004/171094 A1 [0008]
• US 2008/215254 A1 [0009]
• DE 102011055272 A1 [0024]

Claims (22)

Sensor ( 1 ) for the quantitative detection of an analyte in a sample ( 7 ), whereby the sensor ( 1 ) at least one dye ( 2 ), which has an optical behavior which within the sensor ( 1 ) is influenced by the analyte, and a medium ( 3 ) containing the dye ( 2 ), characterized by at least one hollow fiber section ( 4 ), inside which the medium ( 3 ) and by osmolality in the medium ( 3 ) which is greater than a predetermined maximum sample osmolality for which the sensor ( 1 ) is provided. Sensor ( 1 ) according to claim 1, wherein the dye is mixed with a buffer solution. Sensor ( 1 ) according to any one of the preceding claims, wherein the osmolality in the medium ( 3 ) by adding at least one substance to the medium ( 3 ) is set. Sensor ( 1 ) according to any one of the preceding claims, wherein the optical behavior of the at least one dye ( 2 ) contains at least one luminescence or a color or a light reflection or a light absorption or a polarization. Sensor ( 1 ) according to one of the preceding claims, wherein the at least one hollow fiber section ( 4 ) is the portion of a glass hollow fiber. Sensor ( 1 ) according to one of the preceding claims, wherein the material of the at least one hollow fiber section ( 4 ) is permeable to the analyte. Sensor ( 1 ) according to any one of the preceding claims, wherein the sensor ( 1 ) contains a hygroscopic substance. Sensor ( 1 ) according to one of the preceding claims, wherein the at least one hollow fiber section ( 4 ) into a carrier ( 10 ) is embedded. Sensor ( 1 ) according to claim 8, wherein the carrier substance ( 10 ) is gas permeable. Sensor ( 1 ) according to claim 8 or 9, wherein the carrier substance ( 10 ) is hydrophobic. Sensor ( 1 ) according to any one of claims 8 to 10, wherein the carrier substance is a polymer ( 10 ) or a silicone is. Sensor ( 1 ) according to one of claims 1 to 11, wherein ends ( 4a . 4b ) of the at least one hollow fiber section ( 4 ) are open. Sensor ( 1 ) according to one of claims 1 to 11, wherein ends ( 4a . 4b ) of the at least one hollow fiber section ( 4 ) by one stopper ( 4c ) or a cap ( 4d ) are closed. Sensor ( 1 ) according to one of claims 1 to 11, wherein the at least one hollow fiber section ( 4 ) is shaped so that ends ( 4a . 4b ) of the at least one hollow fiber section ( 4 ) are closed. Sensor ( 1 ) according to any one of the preceding claims, wherein the sensor ( 1 ) a plurality of hollow fiber sections ( 4 ) inside which the medium ( 3 ) is located. Method for producing a sensor ( 1 ) for the quantitative detection of an analyte in a sample ( 7 ), comprising the steps of: a) filling at least one hollow fiber ( 5 ) with a medium ( 3 ), the medium ( 3 ) at least one dye ( 2 ), which has an optical behavior which within the sensor ( 1 ) is influenced by the analyte, and wherein the medium ( 3 ) has an osmolality which is greater than a predetermined maximum sample osmolality for which the sensor ( 1 ) is provided; b) dividing the filled at least one hollow fiber ( 5 ) in hollow fiber sections ( 4 ); c) mixing the hollow fiber sections ( 4 ) with a fluid form of a carrier substance ( 10 ); d) distributing the with the carrier substance ( 10 ) mixed hollow fiber sections ( 4 ) over an area; and e) curing the vehicle ( 10 ). The method of claim 16, wherein the dye ( 2 ) is mixed with a buffer solution. A method according to claim 16 or 17, wherein the filling of the at least one hollow fiber ( 5 ) with the medium ( 3 ) Exploits capillary forces, and thereby one end ( 5a ) of the at least one hollow fiber ( 5 ) into a supply of the medium ( 3 ) is immersed. The method of claim 18, wherein a plurality of hollow fibers ( 5 ) in the form of a bundle ( 6 ) with one end ( 5a ) in the stock of the medium ( 3 ) is immersed, after filling the hollow fibers ( 5 ) with the medium ( 3 ) the ends ( 5a . 5b ) of the hollow fibers ( 5 ), and that between the hollow fibers ( 5 ) located medium ( 3 ) is washed off before the hollow fibers ( 5 ) according to step b in hollow fiber sections ( 4 ). Method according to one of claims 16 to 19, wherein the carrier substance is a polymer ( 10 ) or a silicone is. A method according to any one of claims 16 to 20, wherein the dicing of the filled hollow fiber ( 5 ) in hollow fiber sections ( 4 ) happens because hollow fiber sections ( 4 ) of the hollow fiber ( 5 ) are squeezed by a tool which has a temperature at which the material of the hollow fiber ( 5 ) is plastically deformable. Using a sensor ( 1 ) according to claim 15, wherein the plurality of hollow fiber sections ( 4 ) in the sample ( 7 ) is dispersed.

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